Maintaining or adapting family rituals and traditions helps all family members feel a sense of belonging and family identity. For a person with Alzheimer’s, this link with a familiar past is reassuring.

However, there may be a lot of people at celebrations or special events, and this can cause confusion and anxiety for a person with Alzheimer’s. He or she may find some situations easier and more pleasurable than others. Many caregivers have mixed feelings about holidays. They may have happy memories of the past, but they also may worry about the extra demands that holidays make on their time and energy.

These tips from the National Institute on Aging can help you and the person with Alzheimer’s visit and reconnect with family, friends, and neighbors during holidays:

Celebrate holidays that are important to you. Include the person with Alzheimer’s as much as possible.

Set your own limits and be clear about them with others. You do not have to live up to the expectations of friends or relatives. Your situation is different now.

Prepare quiet distractions to use, such as a family photo album.

Involve the person with Alzheimer’s in simple holiday preparations, or have him or her observe your preparations. Observing you will familiarize him or her with the upcoming festivities. Participating with you may give the person the pleasure of helping and the fun of anticipating and reminiscing.

Consider simplifying your holidays around the home. For example, rather than cooking an elaborate dinner, invite family and friends for a potluck. Instead of elaborate decorations, consider choosing a few select items.

Encourage friends and family to visit even if it’s difficult. Limit the number of visitors at any one time, or have a few people visit quietly with the person in a separate room. Plan visits when the person usually is at his or her best.

Prepare quiet distractions to use, such as a family photo album, if the person with Alzheimer’s becomes upset or overstimulated.

Make sure there is a space where the person can rest when he or she goes if the gathering becomes overwhelming. Also, try to stay away from noise, loud conversations, loud music, lighting that is too bright or too dark, and having too much rich food or drink (especially alcohol).

Find time for holiday activities you like to do. If you receive invitations to celebrations that the person with Alzheimer’s cannot attend, go yourself. Ask a friend or family member to spend time with the person while you’re out.

For more information on aging and aging issues, click here.

A release from the Brain Network Labe quotes Jeff Anderson, M.D., Ph.D., associate professor in Radiology at U of U Health and contributing author on the study, as saying, “People with dementia are confronted by a world that is unfamiliar to them, which causes disorientation and anxiety. We believe music will tap into the salience network of the brain that is still relatively functioning.”

Previous work demonstrated the effect of a personalized music program on mood for dementia patients. This study set out to examine a mechanism that activates the attentional network in the salience region of the brain. The results offer a new way to approach anxiety, depression and agitation in patients with dementia. Activation of neighboring regions of the brain may also offer opportunities to delay the continued decline caused by the disease.

For three weeks, the researchers helped participants select meaningful songs and trained the patient and caregiver on how to use a portable media player loaded with the self-selected collection of music.

“When you put headphones on dementia patients and play familiar music, they come alive,” said Jace King, a graduate student in the Brain Network Lab and first author on the paper. “Music is like an anchor, grounding the patient back in reality.”

Using a functional MRI, the researchers scanned the patients to image the regions of the brain that lit up when they listened to 20-second clips of music versus silence. The researchers played eight clips of music from the patient’s music collection, eight clips of the same music played in reverse and eight blocks of silence. The researchers compared the images from each scan.

The researchers found that music activates the brain, causing whole regions to communicate. By listening to the personal soundtrack, the visual network, the salience network, the executive network and the cerebellar and corticocerebellar network pairs all showed significantly higher functional connectivity.

“This is objective evidence from brain imaging that shows personally meaningful music is an alternative route for communicating with patients who have Alzheimer’s disease,” said Norman Foster, M.D., Director of the Center for Alzheimer’s Care at U of U Health and senior author on the paper. “Language and visual memory pathways are damaged early as the disease progresses, but personalized music programs can activate the brain, especially for patients who are losing contact with their environment.”

However, these results are by no means conclusive. The researchers note the small sample size (17 participants) for this study. In addition, the study only included a single imaging session for each patient. It is remains unclear whether the effects identified in this study persist beyond a brief period of stimulation or whether other areas of memory or mood are enhanced by changes in neural activation and connectivity for the long term.

“In our society, the diagnoses of dementia are snowballing and are taxing resources to the max,” Anderson said. “No one says playing music will be a cure for Alzheimer’s disease, but it might make the symptoms more manageable, decrease the cost of care and improve a patient’s quality of life.”

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K.G. Jones, M. Rollins, K. Macnamee, C. Moffit, S.R. Naidu, E. Garcia-Leavitt, R.K. Gurgel, J. Amaro and K.R. Breitenbach at U of U Health and University of Utah, E. Goldberg from the Jewish Family Services of Utah, J.M. Watson from University of Colorado and M.A. Ferguson from Massachusetts General Hospital also contributed to this project. This work received support from A. Scott Anderson and the American Otological Society.

University of Utah Health is the state’s only academic health care system, providing leading-edge and compassionate medicine for a referral area that encompasses 10% of the U.S., including Idaho, Wyoming, Montana and much of Nevada. A hub for health sciences research and education in the region, U of U Health touts a $291 million research enterprise and trains the majority of Utah’s physicians and more than 1,250 health care providers at its Schools of Medicine and Dentistry and Colleges of Nursing, Pharmacy and Health. With more than 20,000 employees, the system includes 12 community clinics and four hospitals — University Hospital; University Neuropsychiatric Institute; Huntsman Cancer Hospital; and the University Orthopaedic Center. For eight straight years, U of U Health has ranked among the top 10 U.S. academic medical centers in the rigorous Vizient Quality and Accountability Study, including reaching No. 1 in 2010 and 2016.

A release from the academy explains that the test involves seeing how fast a person can walk while doing something else at the same time, such as counting backwards or carrying a tray. The study found that the walking test may help differentiate between whether someone has idiopathic normal pressure hydrocephalus or progressive supranuclear palsy.

Idiopathic normal pressure hydrocephalus (iNPH), caused by excess fluid in the brain, can often be reversed but it is usually not diagnosed because it shares symptoms like walking, balance and thinking problems with other neurologic conditions, primarily progressive supranuclear palsy (PSP), which is caused by damage to nerve cells in the brain. There is no cure for PSP, but treatment may help ease symptoms.

The release quotes study author Charlotte Selge, MD, of the Ludwig Maximilian University of Munich in Germany as saying, “It is important that people with idiopathic normal pressure hydrocephalus are accurately diagnosed so they can be treated, and their health can improve. A simple walking test may help determine if a person has iNPH or PSP relatively early in the course of the disease. Our study found that adding another task while someone walks, and evaluating how it affects their walking ability, improves accuracy of the diagnosis.”

The study involved 27 people with iNPH, 38 people with PSP, and 38 healthy people of similar sex and age. Those with PSP and healthy controls had an average age of 69. Those with iNPH had an average age of 72. All participants received a complete neurologic exam, eye exam, MRI as well as thinking and memory tests. All were able to walk at least 30 feet without a walker or cane.

Researchers assessed participants’ manner of walking, or gait, by having all participants walk on a pressure-sensitive carpet that was 22 feet long. People were first asked to walk at three different speeds: slow, their preferred speed and as fast as possible. They were then asked to walk and count backwards at the same time and after that, to walk while carrying a tray.

Researchers found that walking while counting backwards resulted in a greater reduction of walking speed in those with PSP than in those with iNPH. Walking speed was reduced by 34 percent in those with PSP and by 17 percent in those with iNPH. When walking while carrying a tray, gait worsened for those with PSP but actually improved for those with iNPH, which may mean the dual-task test wasn’t challenging enough for those with iNPH, Selge said.

“People with PSP appear to be more sensitive to these dual-task walking tests than people with iNPH,” said Selge.

By just assessing walking, researchers were able to accurately diagnose who had PSP and who had iNPH 82 percent of the time. But when adding both dual-task tests to the assessment, diagnostic accuracy increased to 97 percent.

“Our findings suggest that adding these dual-task tests would be an inexpensive and effective way to improve diagnosis of iNPH,” said Selge. “Future studies may want to increase the complexity of tasks to see if they provide even more accuracy as well as insight into how the two diseases affect gait.”

For years, scientists and physicians have been debating that question.

A new and comprehensive study from Florida State University College of Medicine Associate Professor Antonio Terracciano and colleagues, published in the journal JAMA Psychiatry, has found no evidence to support the idea that personality changes precede MCI or dementia.

“We further found that personality remained stable even within the last few years before the onset of mild cognitive impairment,” Terracciano said.

Terracciano, College of Medicine Associate Professor Angelina Sutin and co-authors from the National Institute on Aging examined data from the Baltimore Longitudinal Study of Aging. The study looked at personality and clinical assessments obtained between 1980 and July 2016 from more than 2,000 individuals who initially showed no cognitive impairment.

About 18 percent of study participants later developed MCI or dementia.

“We compared whether personality change in people who later developed dementia differed from those who remained cognitively normal,” Terracciano said. “Unlike previous research, this study examined multiple waves of self-rated personality data collected up to 36 years before participants developed any sign of dementia.”

What the researchers found is that the trajectory of personality traits did not differ between those who would later develop dementia and those who did not.

While personality change was not an early sign of dementia, Terracciano’s study provides further support that personality traits (including high levels of neuroticism and low levels of conscientiousness) are risk factors for dementia.

For physicians and loved ones, personality changes remain an important consideration in the care of those who have already experienced the clinical onset of MCI or dementia. Increasing apathy, irritability, mood changes and other behavioral symptoms impact quality of life for both patients and their caregivers.

A release from Penn Medicine notes that by using an inexpensive, non-invasive, eye-imaging technique, the scientists found that patients with FTD showed thinning of the outer retina–the layers with the photoreceptors through which we see–compared to control subjects.

The retina is potentially affected by neurodegenerative disorders because it is a projection of the brain. Prior studies have suggested that patients with Alzheimer’s disease and ALS may also have thinning of the retina–although a different part of the retina. Thus, imaging the retina may help doctors confirm or rule out FTD.

The release quotes lead author Benjamin J. Kim, MD, assistant professor of Ophthalmology at Penn’s Scheie Eye Institute, a saying, “Our finding of outer retina thinning in this carefully designed study suggests that specific brain pathologies may be mirrored by specific retinal abnormalities.”

Neurodegenerative diseases in general are challenging to diagnose, and often are confirmed only by direct examination of brain tissue at autopsy. Now that science appears to be on the brink of developing effective treatments for these diseases, the need for better diagnostic methods is becoming acute.

“As we enter an era of disease-modifying treatments for neurodegenerative disorders, it is essential for us to have tools that can identify the specific pathologies accumulating in the brain so that we can administer the appropriate treatments to patients who are likely to benefit,” said study senior author Murray Grossman, MD, a professor of Neurology and director of the Penn FTD Center.

The study included 38 FTD patients enrolled consecutively as they visited the Penn FTD Center, and 44 control subjects who did not have any neurodegenerative disease. The FTD patients were carefully characterized with clinical exams, cerebrospinal fluid biomarkers to exclude Alzheimer’s Disease, and genetic testing. The researchers then employed an eye-imaging technology called spectral-domain optical coherence tomography (SD-OCT), which uses a safe light beam to image tissue with micron-level resolution. SD-OCT imaging is inexpensive, non-invasive, and quick.

Measurements of the retinal layers of the subjects, after adjustments for age, gender, and ethnic background, showed that the outer retinas of the FTD patients were thinner than those in the control subjects. This relative thinning of outer retinas was caused by a thinning of two specific portions of the outer retina, the outer nuclear layer (ONL) and ellipsoid zone (EZ). The ONL of FTD patients was about 10% thinner than controls, and this ONL thinning was the primary source of the outer retina thinning.

The degree of retinal thinning among FTD patients also had a significant tendency to be worse when the patients’ scores on a standard cognition test were lower.

Prior studies have found a loss of optic nerve fibers and associated thinning of the inner retina in a few other neurodegenerative disorders including Alzheimer’s, ALS, and Lewy-body dementia. The new results suggest that FTD manifests in a different way in the structures of the retina, and that this difference, detectable with a retinal imaging test, might help doctors distinguish one disorder from another. FTD is among the most common causes of midlife dementia, and is often misdiagnosed as Alzheimer’s–or vice versa.

FTD itself is not a single disorder but rather a grouping of distinct disorders. The results from the new study suggest that it may be possible to use SD-OCT imaging to distinguish among these FTD subtypes.

Some FTD subtypes involve the abnormal accumulation, in affected brain areas, of thread-like aggregates of a protein called tau. Other FTD subtypes feature abnormal aggregates of a protein called TDP-43. In the study, the Penn researchers used normal clinical criteria to group the FTD patients into probable-tau, probable-TDP-43, and unknown pathology categories. They observed that the outer retinal thinning seemed to occur chiefly in the probable-tau pathology group.

“Prior studies have suggested that tau is expressed in photoreceptor cells, and so we hypothesized that patients with tau brain pathology may have photoreceptor abnormalities,” Kim said. “It was exciting to acquire data that appear to confirm our hypothesis.”

The Penn researchers now plan larger, more conclusive studies to compare retinal measurements among patients who have different FTD subtypes as well as other neurodegenerative diseases.

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Other Penn co-authors include David J. Irwin, Delu Song, Ebenezer Daniel, Jennifer D. Leveque, Aaishah R. Raquib, Wei Pan, Gui-Shuang Ying, Tomas S. Aleman, and Joshua L. Dunaief, all of Penn Medicine at the time of the study.

Funding for the study was provided by the National Institutes of Health.

A release from the association notes that the survey found two out of three caregivers (64 percent) felt isolated or alone in their situation, and more than four in five caregivers (84 percent) would have liked more support with caregiving tasks, particularly from their family. The survey revealed the No. 1 reason people said they did not help with providing care for someone with Alzheimer’s or another form of dementia was they felt as though another family member had already taken on the responsibility (74 percent), followed by their not living in the same area (62 percent).

The release quotes Ruth Drew, Director of Family and Information Services for the Alzheimer’s Association, as saying, “There are currently 15 million Americans providing unpaid care for someone with Alzheimer’s or dementia, and this survey shows that we must alleviate the weight on the shoulders of these individuals. It’s a problem that’s only going to get worse. As life expectancies get longer and the number of older Americans grows rapidly, so too will the number of individuals diagnosed with Alzheimer’s and family members affected.”

In fact, barring the development of a medical breakthrough, the number of Americans age 65 and older with Alzheimer’s is expected to nearly triple by 2050, from 5.5 million to a projected 16 million. Today, someone in the United States develops Alzheimer’s every 66 seconds; by 2050, this will hasten to every 33 seconds.

“Alarmingly, our research also shows that few people are planning for the devastating toll this disease may have on them and their families,” Drew continued. “The burden of Alzheimer’s on society is becoming crushing – and most families are unprepared.” 

Few plan for caregiving costs and decisions

The survey found that people greatly fear becoming a burden to their families as they age, but they are not planning accordingly. For example, 70 percent of people fear being unable to care for themselves or to support themselves financially, but only 24 percent have planned financially for their families in preparation for any future caregiving needs. Moreover, 74 percent of people said they would prefer a paid caregiver, but only 15 percent have financially planned for one – an important consideration, since Alzheimer’s is one of the costliest diseases affecting seniors.

“Very few people are financially prepared for the cost of caring for someone with Alzheimer’s, which is made worse by the fact that most Americans lack adequate savings for retirement, and many have none,” said Beth Kallmyer, MSW, Vice President of Constituent Services for the Alzheimer’s Association. “The added burden of Alzheimer’s care on families that have neither planned for it nor saved for basic retirement needs is going to directly impact them and the public healthcare system. With a large segment of the American population reaching high-risk years for Alzheimer’s, we’re entering a crisis.”

Perhaps surprisingly, survey respondents were even less likely (20 percent) to have discussed their wishes with a spouse or other family member than they were to have made financial plans (24 percent). That lack of communication and cost burden can contribute to family tensions.

“Planning for the costs of care well in advance of need and discussing one’s wishes for future caregiving can help ease the burden on families and avert some of the tensions and family conflicts that may arise following an Alzheimer’s diagnosis,” Kallmyer said.

Alzheimer’s stress can bring families closer or tear them apart

Indeed, findings from the survey show that in some families, Alzheimer’s caregiving fosters strength and support, yet in other families, it tears relationships apart. Relationships between siblings were found to be the most strained, stemming from not having enough support in providing care (61 percent) as well as the overall burden of caregiving (53 percent). Among all caregivers who experienced strain in their relationships, many felt like their efforts were undervalued by their family (43 percent) or the person with the disease (41 percent).

Conversely, 35 percent of survey respondents said caregiving strengthened their relationships with other family members, with two out of three of these respondents reporting that they felt like the experience gave them a better perspective on life. Relationships between spouses/partners were strengthened the most from the experience, with 81 percent believing that “being emotionally there for each other” was a source of strength they drew upon for caregiving.

“Having the support of family is everything when you’re dealt a devastating diagnosis such as Alzheimer’s,” said Jeff Borghoff, 53, a Forked River, New Jersey, resident who has been living with younger-onset Alzheimer’s for two years. “My wife, Kim, has been my rock as we navigate the challenges of Alzheimer’s. It’s easy to want to shut down following a diagnosis, but that’s the time when communication within families is needed most.”

Resources for families

The Alzheimer’s Association can help people learn how to navigate changes in their relationships with family members and friends. In addition to its 24/7 Helpline (800-272-3900), the Association offers various resources for families including:

• A new Alzheimer’s Association infographic, offering specific tips to help families resolve conflicts and cope with Alzheimer’s together
• Guidance on financial and legal planning for Alzheimer’s
• Tips on long-distance caregiving and care coordination to help families better manage caregiver responsibilities
• A video series, featuring insights from people living with the disease on how to navigate the personal and emotional challenges that accompany an Alzheimer’s diagnosis
• A community resource finder that helps families connect with local resources by simply entering their zip code

For these and other resources go to alz.org.

Sometimes becoming a caregiver occurs without a conscious decision. In the early stages of dementia, living at home and even living independently are not only possible but desirable in maintaining the patient’s sense of self and family members – usually a spouse and/or children – are able to provide the necessary care with minimal disruption to their lives. But the cognitive decline associated with Alzheimer’s and other forms of dementia is virtually always progressive and family members have to come to terms with how their roles and relationships will change over time.

In the first stages of caregiving, the primary requirement is for basic information: What are the current needs for feeding and hygiene? Medication? Legal and financial matters? What is the best way to communicate? To deal with behavioral issues? How will the disease progress? The patient’s primary care physician can provide a great deal of information and can steer the family toward community resources for help with issues such as transportation, home-delivered meals, and local daycare programs.

When routines have been established for everyday care, attention must be focused on how to ensure the best possible quality of life for the patient, the family, and especially for the primary caregiver. Here are some tips that will help the patient and prevent caregiving responsibilities from becoming overwhelming.

• Don’t go it alone! Caring for a loved one with dementia is often a 24/7 job with constantly changing (and increasing) responsibilities and primary caregivers are at risk for depression and declining health themselves. Say “yes” to offers of help, even for small things like running errands or providing a meal. Make arrangements for getting a break – whether it’s just to get away for a few hours or for a short vacation. Accept help from family members or contact community agencies that can make recommendations for respite care.
• Keep the patient active, to the extent that it is physically possible. Go for a walk. Enjoy the sunshine, the sounds of birds singing and children playing. Physical activity can decrease anxiety and boredom and can improve sleep. Walking and gentle exercise will also strengthen the leg muscles and help prevent falls.
• Help your loved one make connections: As dementia progresses, the patient increasingly loses a sense of self and of his or her place in the world. But while short-term memory often declines in the early stages of dementia, memories of long ago may be intact and accessible. One way to foster connections is to revive those memories: Look through family photo albums, play or sing old songs, read a favorite book out loud, watch an old movie.
• Foster a connection with animals: Studies have shown that animals have an instinctive ability to help us heal and that a connection with animals can help reduce stress, improve confidence, and enhance overall well-being for those affected by early-stage dementia. Arrange a visit with a cat or dog or look into a structured workshop that supports non-riding interaction with horses.

Providing care for someone with dementia takes a tremendous toll on the physical and emotional health of the primary caregiver. Caregivers must take care of themselves as well as caring for their loved one. And with the dramatic growth of the elder population and the associated growth in the number of people with dementia, we must go beyond medicine to find ways to enhance the quality of life for patients and caregivers.

Elizabeth Landsverk, MD, is founder of ElderConsult Geriatric Medicine, a house-calls practice in the San Francisco Bay Area that addresses the challenging medical and behavioral issues often facing older patients and their families. Dr. Landsverk is board-certified in internal medicine, geriatric medicine and palliative care and is an adjunct clinical professor at Stanford University Medical School. http://www.elderconsult.com

This research builds upon previous studies demonstrating that art, music, and other similar therapies can effectively reduce symptoms of dementia without medication. By using tablet devices to employ these therapies, however, patients and providers also benefit from a computer’s inherent flexibility.

The release quotes Vania as saying, “The biggest advantage is versatility. We know that art therapy can work, music therapy can work. The tablet, however, gives you the option of switching from one app to another easily, modifying the therapy seamlessly to suit the individual. You don’t need to invest in new equipment or infrastructure.”

Researchers loaded a menu of 70 apps onto the tablets for the study. The apps were freely available on iTunes and varied greatly in their cognitive complexity–from an app that displayed puppy photos to one that featured Sudoku puzzles.

The researchers found that tablet use was safe for every patient, regardless of the severity of their dementia, and that with proper supervision and training, the engagement rate with the devices was nearly 100 percent. The study also found that the tablets demonstrated significant effectiveness in reducing symptoms of agitation, particularly–but not exclusively–among patients with milder forms of dementia.

Vahia cited several examples of the tablet’s potential to improve a patient’s condition. One particular patient, who only spoke Romanian, was very withdrawn and irritable, and medications were ineffective in controlling his symptoms.

“We started showing him Romanian video clips on YouTube, and his behavior changed dramatically and instantaneously,” said Vahia. “His mood improved. He became more interactive. He and his medical support team also started using a translation app so that staff could ask him simple questions in Romanian, facilitating increased interaction. These significant improvements are a clear testament of the tablet’s potential as a clinical tool.”

Based on such promising outcomes, the Geriatric Psychiatry Outpatient Services clinical team is expanding the use of tablet devices as a means to control agitation in dementia patients at McLean. This will allow researchers to develop more robust data and expand the scope of the study, including a focus on specific clinical factors that may impact how patients with dementia engage with and respond to apps.

Scientists believe that many factors influence when Alzheimer’s disease begins and how it progresses. The more they study this devastating disease, the more they realize that genes play an important role. Research conducted and funded by the National Institute on Aging (NIA) at the National Institutes of Health (NIH) and others is advancing our understanding of Alzheimer’s disease genetics.

The Genetics of Disease

Some diseases are caused by a genetic mutation, or permanent change in one or more specific genes. If a person inherits from a parent a genetic mutation that causes a certain disease, then he or she will usually get the disease. Sickle cell anemia, cystic fibrosis, and early-onset familial Alzheimer’s disease are examples of inherited genetic disorders.

In other diseases, a genetic variant may occur. A single gene can have many variants. Sometimes, this difference in a gene can cause a disease directly. More often, a variant plays a role in increasing or decreasing a person’s risk of developing a disease or condition. When a genetic variant increases disease risk but does not directly cause a disease, it is called a genetic risk factor.

Identifying genetic variants may help researchers find the most effective ways to treat or prevent diseases such as Alzheimer’s in an individual. This approach, called precision medicine, takes into account individual variability in genes, environment, and lifestyle for each person.

Alzheimer’s Disease Genetics

Alzheimer’s disease is an irreversible, progressive brain disease. It is characterized by the development of amyloid plaques and neurofibrillary, or tau, tangles; the loss of connections between nerve cells (neurons) in the brain; and the death of these nerve cells. There are two types of Alzheimer’s—early-onset and late-onset. Both types have a genetic component.

What Are DNA, Chromosomes, and Genes?

Genetic mutations in a cell can lead to abnormal proteins and, in turn, diseases such as early-onset Alzheimer’s.

The nucleus of almost every human cell contains a “blueprint” that carries the instructions a cell needs to do its job. The blueprint is made up of DNA (deoxyribonucleic acid), which is present in long strands that would stretch to nearly 6 feet in length if attached end to end. The DNA is packed tightly together with proteins into compact structures called chromosomes. Normally, each cell has 46 chromosomes in 23 pairs, which are inherited equally from a person’s biological parents. The DNA in nearly all cells of an individual is identical.

Each chromosome contains many thousands of segments, called genes. People inherit two copies of each gene from their parents, except for genes on the X and Y chromosomes, which, among other functions, determine a person’s sex. The genes “instruct” the cell to make unique proteins that, in turn, dictate the types of cells made. Genes also direct almost every aspect of the cell’s construction, operation, and repair.

Even slight changes in a gene can produce a protein that functions abnormally, which may lead to disease. Other changes in genes may increase or decrease a person’s risk of developing a particular disease.

Early-Onset Alzheimer’s Disease

Early-onset Alzheimer’s disease occurs in people age 30 to 60 and represents less than 5 percent of all people with Alzheimer’s. Most cases are caused by an inherited change in one of three genes, resulting in a typle known as early-onset familial Alzheimer’s disease, or FAD. For others, the disease appears to develop without any specific, known cause.

A child whose biological mother or father carries a genetic mutation for early-onset FAD has a 50/50 chance of inheriting that mutation. If the mutation is in fact inherited, the child has a very strong probability of developing early-onset FAD.

Early-onset FAD is caused by any one of a number of different single-gene mutations on chromosomes 21, 14, and 1. Each of these mutations causes abnormal proteins to be formed. Mutations on chromosome 21 cause the formation of abnormal amyloid precursor protein (APP). A mutation on chromosome 14 causes abnormal presenilin 1 to be made, and a mutation on chromosome 1 leads to abnormal presenilin 2.

Each of these mutations plays a role in the breakdown of APP, a protein whose precise function is not yet fully understood. This breakdown is part of a process that generates harmful forms of amyloid plaques, a hallmark of the disease.

Critical research findings about early-onset Alzheimer’s have helped identify key steps in the formation of brain abnormalities typical of the more common late-onset form of Alzheimer’s. Genetics studies have helped explain why the disease develops in people at various ages.

NIA-supported scientists are continuing research into early-onset disease through the Dominantly Inherited Alzheimer Network (DIAN), an international partnership to study families with early-onset FAD. By observing the Alzheimer’s-related brain changes that occur in these families long before symptoms of memory loss or cognitive issues appear, scientists hope to gain insight into how and why the disease develops in both its early- and late-onset forms.

In addition, an NIA-supported clinical trial in Colombia, South America, is testing the effectiveness of an amyloid-clearing drug in symptom-free volunteers at high risk of developing early-onset FAD.

For more information, see NIA’s Early-Onset Alzheimer’s Disease: A Resource List.

Late-Onset Alzheimer’s Disease

Most people with Alzheimer’s have the late-onset form of the disease, in which symptoms become apparent in the mid-60s and later. The causes of late-onset Alzheimer’s are not yet completely understood, but they likely include a combination of genetic, environmental, and lifestyle factors that affect a person’s risk for developing the disease.

Researchers have not found a specific gene that directly causes the late-onset form of the disease. However, one genetic risk factor—having one form of the apolipoprotein E (APOE) gene on chromosome 19—does increase a person’s risk. APOE comes in several different forms, or alleles:

• APOE ε2 is relatively rare and may provide some protection against the disease. If Alzheimer’s disease occurs in a person with this allele, it usually develops later in life than it would in someone with the APOE ε4 gene.
• APOE ε3, the most common allele, is believed to play a neutral role in the disease—neither decreasing nor increasing risk.
• APOE ε4 increases risk for Alzheimer’s disease and is also associated with an earlier age of disease onset. A person has zero, one, or two APOE ε4 alleles. Having more APOE ε4 alleles increases the risk of developing Alzheimer’s.

APOE ε4 is called a risk-factor gene because it increases a person’s risk of developing the disease. However, inheriting an APOE ε4 allele does not mean that a person will definitely develop Alzheimer’s. Some people with an APOE ε4 allele never get the disease, and others who develop Alzheimer’s do not have any APOE ε4 alleles.

Using a relatively new approach called genome-wide association study (GWAS), researchers have identified a number of regions of interest in the genome (an organism’s complete set of DNA, including all of its genes) that may increase a person’s risk for late-onset Alzheimer’s to varying degrees. By 2015, they had confirmed 33 regions of interest in the Alzheimer’s genome.

A method called whole genome sequencing determines the complete DNA sequence of a person’s genome at a single time. Another method called whole exome sequencing looks at the parts of the genome that directly code for the proteins. Using these two approaches, researchers can identify new genes that contribute to or protect against disease risk. Recent discoveries have led to new insights about biological pathways involved in Alzheimer’s and may one day lead to effective interventions.

Genetic Testing

A blood test can identify which APOE alleles a person has, but results cannot predict who will or will not develop Alzheimer’s disease. It is unlikely that genetic testing will ever be able to predict the disease with 100 percent accuracy, researchers believe, because too many other factors may influence its development and progression.

Currently, APOE testing is used in research settings to identify study participants who may have an increased risk of developing Alzheimer’s. This knowledge helps scientists look for early brain changes in participants and compare the effectiveness of treatments for people with different APOE profiles. Most researchers believe that APOE testing is useful for studying Alzheimer’s disease risk in large groups of people but not for determining any one person’s risk.

Genetic testing is used by researchers conducting clinical trials and by physicians to help diagnose early-onset Alzheimer’s disease. However, genetic testing is not otherwise recommended.

Epigenetics: Nature Meets Nurture

Scientists have long thought that genetic and environmental factors interact to influence a person’s biological makeup, including the predisposition to different diseases. More recently, they have discovered the biological mechanisms for those interactions. The expression of genes (when particular genes are “switched” on or off) can be affected—positively and negatively—by environmental factors at any time in life. These factors include exercise, diet, chemicals, or smoking, to which an individual may be exposed, even in the womb.

Epigenetics is an emerging science focused on how and when particular genes are turned on or off. Diet and exposure to chemicals in the environment, among other factors, can alter a cell’s DNA in ways that affect the activity of genes. That can make people more or less susceptible to developing a disease.

There is emerging evidence that epigenetic mechanisms contribute to Alzheimer’s disease. Epigenetic changes, whether protective, benign, or harmful, may help explain, for example, why one family member develops the disease and another does not. Scientists are learning more about Alzheimer’s-related epigenetics, with the hope of developing individualized treatments based on epigenetic markers and their function.

Research Questions

Discovering all that we can about the role of Alzheimer’s disease genetic risk and protective factors is an important area of research. Understanding more about the genetic basis of the disease will help researchers to:

• Answer a number of basic questions—What makes the disease process begin? Why do some people with memory and other thinking problems develop Alzheimer’s while others do not?
• Determine how genetic risk and protective factors may interact with other genes and lifestyle or environmental factors to affect Alzheimer’s risk in any one person.
• Identify people who are at high risk for developing Alzheimer’s so they can benefit from new interventions and treatments as soon as possible.
• Focus on new prevention and treatment approaches.

Major Alzheimer’s Genetics Research Efforts Underway

The National Institute on Aging supports several major genetics research programs.

• The Alzheimer’s Disease Sequencing Project (ADSP) is an innovative collaboration between NIA and the National Human Genome Research Institute, both part of NIH. The first phase of the project determined the order of all 3 billion letters in the individual genomes of 580 participants. It also generated whole exome sequencing data for an additional 11,000 volunteers.
• The Alzheimer’s Disease Genetics Consortium is a collaborative effort to collect and analyze genetic data from thousands of families around the world to identify genes associated with an increased risk of developing late-onset Alzheimer’s.
• The Late-Onset Alzheimer’s Disease Genetics Study is gathering and analyzing genetic and other information from 1,500 or more families in the United States with two or more members who have late-onset Alzheimer’s.
• The International Genomic Alzheimer’s Project (IGAP) is comprised of four consortia in the United States and Europe that have been working together since 2011 on genome-wide association studies (GWAS) involving thousands of DNA samples and shared data sets. In a study of more than 74,000 individuals, IGAP recently reported the identification of 19 novel regions of interest that are associated with the disease.
• The Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) is a national genetics data repository that gives investigators access to data to study the genetics of late-onset Alzheimer’s disease.
• The National Cell Repository for Alzheimer’s Disease (NCRAD) is a national resource that helps researchers find genes that increase the risk of Alzheimer’s by providing biological samples and data.

Volunteers are critical to Alzheimer’s disease genetics research. The more genetic information that researchers can gather and analyze from individuals and families—both healthy volunteers and those who may be at risk—the more clues they will have for finding additional risk-factor genes.

To learn more about Alzheimer’s genetics studies, contact NCRAD toll-free at 1-800-526-2839 or visit http://ncrad.iu.edu.

To learn more about volunteering for Alzheimer’s clinical trials and studies, visit www.nia.nih.gov/alzheimers/volunteer.

This information originally appeared on the National Institute on Aging web site.

How are spouses, adult children, and other family members affected by Alzheimer’s disease when the patient no longer recognizes his or her own family or believes a son or daughter to be the spouse? Does this lack of recognition seduce family members to hold on more tightly with the hope that one day a loved one may show a glimmer of recollection? Do family members feel disconnected and less committed to continue to visit a loved one who no longer remembers or feels connected to them?  Does this lack of recognition of marriage by a spouse with memory loss raise the option for the healthy spouse to pursue a companion or even another lifelong partner?

I am commonly asked by caregivers of persons with dementia or Alzheimer’s disease if their experiences are unusual. I respond that with a diagnosis of memory loss there is no usual, meaning that each journey is unlike another and that there is no crystal ball to predict the future. This uncertainly is the component that results in stress and anxiety for families because many feel they have no control over the situation and delay making a plan for care.

The planning component is critical for persons diagnosed with memory loss especially if the memory loss is diagnosed early, if the individual is aware of the diagnosis, and is able to express wishes and desires in writing to family and to a spouse. This is the time to appoint a medical and financial power of attorney, to finalize a living will, and to establish a will or a trust. This is also the time to have “what if” discussions with family.  What if the time comes that a husband or wife can no longer provide care at home? What if a care community becomes a necessity? In what type of community would the individual with memory loss choose to live? Are there financial resources to pay for care or is Medicaid a likely payer? What are the wishes for burial or cremation?

These practical questions should be a priority in addition to the more difficult discussions of creating memories today so that when memory does fail, the family has something tangible by which to remember a loved one: photographs, family recipes, discussion about the family tree, my wishes for what happens when I don’t recognize my wife, brother, sister or children. Denial and delay of these discussions—not talking or thinking about end of life— permits family members to avoid these all important but difficult conversations that result in conflict later as the disease progresses.

This is what I hear from caregivers of loved ones who have been diagnosed: “My husband wants me to take him skiing and point him in the direction of a steep cliff.”

I  hear other individuals say “put me somewhere and go on with your life.” Those who love the outdoors desire to go camping and have an adventure from which they don’t return. One might wonder how sincere these statements are. If there truly was a change in situation, would the request change to desiring care rather than ending an unpleasant condition.

The conversation of what do I want for myself (and my spouse), especially for individuals with memory loss, is important and should be held early before memory loss or a chronic or terminal disease advances. Held when logic rather than when emotion or guilt become entrenched and change the conversation. I recommend placing these wishes in writing as children and other family members typically place guilt on a spouse or the responsible caregiver for making decisions they may disagree with yet decisions that represent the wishes of the care receiver.  How many times after a loved one passes away do families argue over cremation or burial, service or no service, and last wishes; more often than families might imagine.

If you were the person diagnosed with dementia or Alzheimer’s, what type of life would you wish for your spouse if you knew that there will be a time when the marriage relationship focuses solely on care tasks related to the advancement of the disease? Tasks like incontinence care, feeding, and constant one-on-one companionship. What if your care needs required that your spouse identify others—in home caregivers or a care community—to provide hands on care because your spouse alone cannot provide the level of care and support that you require? What happens to the marriage when you are no longer able to recognize your spouse or to find the words to carry on a meaningful conversation? A marriage where your spouse grieves your loss as your memory slips away day by day and is isolated in the role of caregiver and lonely because of the responsibility and duty of care?

What would you want for your spouse? The dilemma of a community spouse caring for a spouse with dementia or Alzheimer’s is rarely discussed. Marriage is supposed to be forever. Many spouses in a marriage affected by dementia or Alzheimer’s disease feel guilty if they seek out companionship and loudly hear from others that they should remain dedicated to their marriage regardless of the condition of the spouse diagnosed with memory loss.  This, like the prediction of what will happen as the result of a diagnosis of memory loss, is an unusual situation with no usual. There are no right or wrong answers.

Abandoning a spouse diagnosed with dementia or memory loss is a very different situation versus a spouse committed to ensure that a loved one receives care—but who seeks out companionship or love outside of the marital relationship. Many believe in the marital commitment to care for a spouse. I have personally witnessed the challenges of this situation for the caregiver spouse who is committed to a loved one yet emotionally and physically exhausted from being a 24/7 caregiver and having no social life. I have also witnessed the loneliness and isolation of a spouse caring for a loved one with dementia or Alzheimer’s disease who then becomes as ill as the spouse for whom care is provided.

Research affirms the benefits of continued social activity and connection for caregivers; this includes marital caregivers. How might society address the challenge of the healthy spouse caring for a spouse with a diagnosis of memory loss with no recollection of the marriage? Should the legal profession begin including direction in medical power of attorney or other marital agreements regarding “at the time I need significant care, I wish for my own care x, y, z and I wish for my spouse a, b, c?”

Just like the concept of a life review to create an ethical will that shares values, blessings, life’s lessons, hopes and dreams and love and forgiveness, do we need a specialty legal document surrounding marriage and caregiving when there is no spousal recognition or when care requires long term placement that risks elimination of all marital savings and finances?

Alzheimer’s disease appears daily in the press; it is a dreaded diagnoses. Caregiving, while well publicized, is not a subject of awareness until the need arises and one becomes a caregiver. Care relationships are filled with denial and avoidance of planning. Society avoids the subjects of illness and death.

Might we be better prepared for caregiving and aging if there were more discussion of the process of aging in the community; whether in churches, medical offices, or community groups? Might we be better prepared for responding to the challenges that result from caregiving and how these affect family relationships including marriages if this was part of a school curriculum or workplace support program? Might these broader discussions—if discussed earlier in life—have a positive impact on daily health and retirement planning so that when caregiving becomes a reality there are fewer crises and more focus on making memories?